title: In vitro and in vivo effects of metformin on human adipose tissue adiponectin.
abstract: OBJECTIVE
  The effects of metformin on adiponectin production are controversial and have never been investigated in human adipose tissue. We analysed whether metformin modulates, in vitro and in vivo, gene expression, protein content, and secretion of adiponectin.
  
  
  METHODS
  For the in vitro study, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples from 5 non-diabetic obese patients were collected. For the in vivo investigation, 22 obese patients were randomly assigned to metformin+lifestyle (ML) or placebo+lifestyle (PL) intervention. SAT specimens and blood samples were collected before and after the intervention in both groups.
  
  
  RESULTS
  In in vitro experiments, treatment with metformin increased the expression and secretion of adiponectin in SAT, but not in VAT explants. In the in vivo study, a significant increase in adiponectin and a decreased expression of a macrophage activation marker (CD68) were observed only in SAT of the ML group.
  
  
  CONCLUSIONS
  These results demonstrate that metformin is able to up-regulate adiponectin gene expression, both in vivo and in vitro, and to stimulate adiponectin protein secretion from human SAT in vitro. It could be hypothesised that metformin-induced adiponectin increase within adipose tissue may have an unexpected role in the reduction of local inflammation.
authors.affiliation: Department of Medical Sciences and Rehabilitation, University of Milan, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zulian
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cancello
authors.forename: Andrea
authors.initials: A
authors.lastname: Girola
authors.forename: Luisa
authors.initials: L
authors.lastname: Gilardini
authors.forename: Luisella
authors.initials: L
authors.lastname: Alberti
authors.forename: Marina
authors.initials: M
authors.lastname: Croci
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Micheletto
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Danelli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Invitti
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008019:Life Style; D008687:Metformin / Q000494:pharmacology*; D009765:Obesity / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism
chemical_list: D052242:Adiponectin; D007004:Hypoglycemic Agents; D008687:Metformin